Low-Grade Fibromyxoid Sarcoma: Incidence, Treatment Strategy of Metastases, and Clinical Significance of the FUS Gene

Aim. The aim of this study was to assess the incidence of low-grade fibromyxoid sarcoma (LGFMS), present treatment results of metastatic LGFMS, and investigate the clinical significance of the FUS gene rearrangement. Methods. This study included 14 consecutive LGFMS patients treated at the Aarhus Sarcoma Centre in 1979–2010. Fluorescent in situ hybridization (FISH) analysis for FUS break-apart was performed for all patients. Results. The incidence of LGFMS was 0.18 per million, representing 0.6% of all soft tissue sarcomas. Four patients needed multiple biopsies/resections before the correct diagnosis was made. Four patients experienced local recurrence, and three patients developed metastases. The treatment of metastatic LGFMS varied from multiagent chemotherapy to repeated, selective surgery of operable metastases. The best response to chemotherapy was short-term stabilization of disease progression, seen with Trabectedin. The prevalence of the FUS break-apart was 21.4%. We found no significant difference in clinical characteristics and outcomes in correlation with the FUS break-apart. Conclusion. LGFMS is a rare disease with multiple challenges. The FUS break-apart was not associated with local recurrence or metastases in our study. To date the only treatment resulting in disease-free periods is surgery; however further investigation into the management of metastatic LGFMS is necessary. 1. Introduction Low-grade fibromyxoid sarcoma (LGFMS) is characterized by its relatively benign histological appearance with spindle cells in a whorling pattern, as well as collagenized and myxoid areas [1, 2]. The heterogeneous histological appearance makes the diagnosis challenging. In spite of the low-grade and benign histological appearance, early studies of retrospectively diagnosed LGFMS have shown a distinct biological behaviour, with a relatively high and atypical metastasizing potential, making the correct diagnosis of LGFMS important [1, 2]. Likely due to the difficulties in diagnosing LGFMS, the incidence has not been previously described. LGFMS raises many clinical challenges. The metastatic potential raises the question whether surgery alone, which is standard treatment for other low-grade soft tissue sarcomas, is enough. The atypical metastatic potential, with atypical sites of metastases and relapses long after primary treatment, affects the choice of the best imaging method as well as the optimal duration of followup. The lack of sensitivity to radiotherapy and chemotherapy makes it important to identify patients with high risk of metastasis and obtain